AUTHOR=Chaumond Emmanuel , Peron Sandrine , Daniel Nathalie , Le Gouar Yann , Guédon Éric , Williams David L. , Le Loir Yves , Jan Gwénaël , Berkova Nadia 

TITLE=Development of innate immune memory by non-immune cells during Staphylococcus aureus infection depends on reactive oxygen species

JOURNAL=Frontiers in Immunology

VOLUME=Volume 14 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1138539

DOI=10.3389/fimmu.2023.1138539

ISSN=1664-3224

ABSTRACT=The mechanisms underlying innate immune memory (trained immunity) comprise epigenetic reprogramming of transcriptional pathways associated with alterations of intracellular metabolism. While the mechanisms of innate immune memory carried out by immune cells are well characterized, such processes in non-immune cells, are poorly understood.
The opportunistic pathogen, Staphylococcus aureus, is responsible for a multitude of human diseases, including pneumonia, endocarditis and osteomyelitis, as well as animal infections, including chronic cattle mastitis that are extremely difficult to treat. An induction of innate immune memory may be considered as a therapeutic alternative to fight S. aureus infection.
In the current work, we demonstrated the development of innate immune memory in non-immune cells during S. aureus infection. We observed that training of human osteoblast-like MG-63 cells and lung epithelial A549 cells with β-glucan increased IL-6 and IL-8 production upon a secondary stimulation with S. aureus, concomitant with histones modifications, suggesting epigenetic reprogramming. An addition of the ROS scavenger N-Acetylcysteine, NAC, prior to β-glucan pretreatment followed by an exposure to S. aureus, resulted in decreased IL-6 and IL-8 production, thereby supporting the involvement of ROS in the induction of innate immune memory. In addition to known inducers, probiotics may represent good candidates for the induction of innate immune memory. Exposure of cells to Lactococcus lactis resulted in increased IL-6 production upon a secondary stimulation with S. aureus suggesting the ability of this beneficial bacterium to induce innate immune memory. The current study improves our understanding of innate immune memory by non-immune cells and may help the development of alternative therapeutic approaches for the prevention of S. aureus infection.